Terminal erythroid differentiation in the K-562 cell line by 1-beta-D-arabinofuranosylcytosine: accompaniment by c-myc messenger RNA decrease.

Two erythroid markers, acetylcholinesterase and hemoglobin, can be reversibly induced in the K-562 cell line after sodium butyrate treatment. In the present paper we show that 1-beta-D-arabinofuranosylcytosine (ara-C), induces the coordinate, irreversible expression of these two erythroid markers. This induction occurs at an ara-C concentration (0.05 mM) that results in K-562 cytostasis and is accompanied by deep morphological changes of cells. The differentiated phenotype is independent of the K-562 cell clone used [K-562, K-562 (S), K-562 (S)P] and is associated with the loss of cell renewal capacity. Continuous presence of the inducer is not necessary to achieve terminal differentiation. In contrast to what is seen for other inducers (sodium butyrate and hemin), one of the early effects of ara-C treatment is the marked decrease of c-myc mRNA expression after the first 4 hours of induction, whereas N-ras and histone 4 expression remain constant during the first 48 h. Our results suggest that ara-C treatment can irreversibly activate the erythroid differentiative program of K-562 cells.

Unusual Ph translocations in CML: four new cases.

Four variants of the Ph chromosome translocation in chronic myelogenous leukemia (CML) patients are described. Two had an unusual simple translocation involving chromosomes #7 and #17. In two cases, the translocation, aside from involving #9 and #22, involved a third chromosome, chromosome #6 and chromosome #11, respectively. Three cases showed also karyotypic evolution during the blastic phase of the disease: in two cases, a new reciprocal translocation was found that involved a chromosome #9 at band q34. The clinical and cytogenetic significance of these results is briefly discussed.

Masked Philadelphia chromosome caused by translocation (9;11;22).

In a patient with chronic myelocytic leukemia (CML), chromosome analysis revealed a translocation involving chromosomes No. 9, 11, and 22, with three break points, thus giving origin to a so-called "masked" Philadelphia chromosome (Ph1). A review of similar cases reported in the literature indicates that a masked Ph1 is very rare, that the chromosomes involved vary from case to case, and that in most cases the pattern of the rearrangement is quite different from that of two- and three-chromosome variant Ph1 translocations.

Fibroblastoid colony-forming cells in myeloproliferative disorders.

The properties of human bone marrow fibroblastoid colonies (CFU-F) were studied in normal subjects and in patients with myeloproliferative disorders. Colony incidence was within normal values in all groups of patients analyzed except for myelodisplastic syndromes, with higher mean value. The growth rate of CFU-F is inversely related to the initial colony-forming efficiency both in normal subjects and in patients. Direct correlation between CFU-F and granulocyte-macrophage colony-forming unit (GM-CFU) was detected only in normal subjects, but lacked in patients. Higher number of CFU-F was observed in subjects with increased incidence of bone marrow megakaryocytes or peripheral blood platelets, irrespective of the underlying disorders and the platelet-derived growth-factorenhanced cloning efficiency of bone marrow fibroblasts.

Coincidence between fragile site expression and interstitial deletion of chromosome 11 in a case of myelofibrosis.

Cytogenetic examination of multiple peripheral blood cultures of a patient with myelofibrosis with myeloid metaplasia revealed the presence of an interstitial deletion of the long arm of chromosome 11, del(11)(q13q21). A folic acid dependent fragile site fra(11)(q13) was found in about 12% of the cells. The possible correlation between constitutional fragile site and acquired chromosomal alteration is discussed briefly.

Marrow colony stimulating activity in chronic myelogenous leukemia.

Colony stimulating activity (CSA) from bone marrow adherent cells was tested in various myeloproliferative disorders in comparison with chronic myelogenous leukemia (CML). A higher level of medullary CSA was found in acute leukemias with monoblastic component, as contrasted with low values in other acute non lymphocytic leukemias (ANLL). In CML, while the majority of patients had CSA values within normal interval, few patients had consistently higher level of this activity. Comparative analysis of growth pattern in agar or in liquid culture suggests that significant increase in medullary CSA production can be related to an abnormal regulation of granulopoiesis.

Urinary granulopoietic activity in chronic myelogenous leukemia: follow-up and correlation with various phases of the disease.

Daily urinary colony-stimulating factor (CSF) output was tested in 16 patients with chronic myeloid leukemia, 12 of which were in stable phase and 4 in blast crisis of the disease. The CSF of stable-phase patients varied within normal range, while all patients in blast crisis had values lower than normal. Also the number of CFUC ranged within normal values in stable-phase patients, while no colony growth was detectable in blast-crisis patients. Sequential studies (28 or 11 months) of 2 patients revealed an inverse relation between daily urinary CSF and presence of peripheral immature or blast cells in the patient in stable or blast phase, respectively.

Urinary colony-stimulating factor in acute leukemia follow-up and correlation with various phases of the disease.

Urinary colony-stimulating factor (CSF) was assayed in 19 patients with various leukemias and was monitored in various phases of acute leukemia in 3 patients. Significantly higher CSF levels were found at the onset of leukemia with a monoblastic component. Continuous monitoring of CSF in a patient with acute myelomonocytic leukemia revealed a decrease in CSF level during the remission phase, followed by a rebound to high levels preceding the clinical and hematological relapse. Concomitantly, a colony-inhibitory factor (CIF) was detected. Both CSF and CIF of this patient were isolated and partially characterized.

Karyotype evolution in a case of chronic myelogenous leukemia with an unusual Philadelphia chromosome translocation, t(4;22), and an additional translocation, t(3;5).

A patient with chronic myelogenous leukemia was found, at the time of diagnosis, to have an unusual Philadelphia chromosome translocation, t(4;22) (q35;q11) and an additional previously unreported translocation, t(3;5) (q27;q22). The blastic crisis, which occurred after 14 months, was characterized by the appearance of i(17q). Ten months later, two different hyperdiploid cell lines with 50 chromosomes were found in about 20% of the metaphases examined.

Preparation of colony stimulating activity from human leukemic urine: hydrophobic chromatography on propylamine-agarose.

Urinary colony stimulating factor (CSF) from human leukemic urine is retained on propylamine-agarose hydrophobic chromatography; about 70% of total activity is eluted by the addition of 1 M NaCl with significant increase in specific activity. Incomplete binding of urinary CSF to this resin further confirm that biological activity is a heterogeneous pool of different molecular species. Analysis of the macro- and microscopic composition of colonies indicates that CSF resulting from this purification step maintains the ability to stimulate both granulocytic and macrophage progenitors.